A patient with a complete spinal cord injury, resulting in the loss of sensory and motor function below the level of the injury, has progressively regained the ability to move their legs voluntarily and stand without the use of spinal cord epidural stimulation, according to a study published in Scientific Reports. Previous tests involving four patients with chronic clinically motor complete spinal cord injury found that the use of lumbosacral spinal cord epidural stimulation (scES) — an approach that sends electrical signals to motor neurons — and activity-based training led to the participants recovering the ability to stand when the scES device was activated. In addition, delivering scES enabled these individuals to perform relatively fine volitional lower limb movements. Susan Harkema and colleagues, from the University of Louisville in the US, reported that on completion of the original study, one participant was recruited to perform additional activity-based training with scES at home and in the laboratory. Over the course of the next 44 months, the authors found that the participant recovered substantial voluntary lower limb motor control and the ability to stand independently, without the use of scES. The authors noted that the ability to stand independently was observed for the first time after a training period that differed substantially from previous training periods in terms of the frequency of the training, the tasks trained and the volitional involvement of the research participant. The authors suggested that future studies should attempt to better understand the influence of different activity-based training components on the physiological adaptations resulting in motor function improvements after severe spinal cord injury.

Computational simulations suggest multiple sclerosis is a single disease

New research out of the University of Barcelona supports the idea that multiple sclerosis (MS), which has widely varying symptoms and progression in different patients, is nonetheless a single disease with common underlying mechanisms. The findings are published in PLOS Computational Biology. MS is an autoimmune disease that can cause a variety of problems, including blurred vision, memory problems and paralysis. Symptoms and patterns of disease progression over time can vary between patients, leading to suggestions that MS may consist of two or more different diseases. The researchers hypothesised that MS is a single disease with multiple results in patients, all driven by the same underlying biological mechanism: immune system attack of the protective fibres shielding nerve cells and loss of the axons used by nerve cells to communicate with each other. The researchers developed a mathematical model of MS based on experimental data from 66 patients who had been followed for up to 20 years. Using the model, they were able to perform computational simulations of the different known biological processes involved in the disease. To test the validity of the model, the scientists ran simulations using data from a second group of 120 patients with MS. They found that, by changing the intensity of the underlying biological processes involved in MS at distinct times, they were able to successfully reproduce the variability of disease courses seen in these patients. These results support the hypothesis that all the symptoms and disease courses observed in patients with MS are produced by the same underlying mechanisms that damage nerve cells over time. This implies that, even though it may follow different patterns, MS will worsen over time for all patients. “This concept has significant therapeutic implications and will drive the development of new therapies because it implies that MS will produce significant disability if had for enough time in all patients,” says co-author Dr Pablo Villoslada. “Indeed, preventing relapses, although very important, will not be enough to achieve good control of the disease.”

Afternoon heart surgery linked to better patient outcomes

Outcomes for open heart surgery may be improved by moving surgery to the afternoon, rather than in the morning, according to a study published in The Lancet which identifies a link between a person’s circadian clock and their risk of heart damage and major cardiac events after heart surgery. The study also provides early insights into the mechanism behind this link, identifying nearly 300 genes linking the circadian clock to heart damage. After open heart surgery, some patients may develop heart damage affecting the heart’s ability to pump blood, resulting in poor outcomes, including onset of heart failure and a heightened risk of death. Previous research has suggested that cardiovascular events such as myocardial infarction which happen in the morning may be associated with a higher risk of the damage, compared with afternoon events, but reasons have remained unclear. The Lancet study, out of the University of Lille in France, included an observational study looking at the association between time of day of surgery and outcomes, a randomised controlled trial (RCT) to investigate whether there was a causal link between time of day of surgery and outcomes, and a human tissue analysis to identify genes involved in the circadian effect on heart surgery. In the observational study, which ran for 6 years, researchers tracked the medical records of 596 people who had heart valve replacement surgery (half had surgery in the morning, half in the afternoon) for 500 days to monitor for any major cardiac events, such as a heart attack, heart failure or death from heart disease. Patients who had afternoon surgery had a 50% lower risk of a major cardiac event compared with people who had surgery in the morning (28/298 [9.4%] compared with 54/298 [18.1%]) – equating to one major event avoided for every 11 patients who had afternoon surgery. In the RCT, which took place from January 2016 to February 2017, 88 patients were randomly scheduled for heart valve replacement surgery in the morning or afternoon and their health was monitored until they left hospital. There were no deaths in either group and the average time in hospital was 12 days. Patients who had afternoon surgery had lower levels of heart tissue damage after surgery compared with patients who had morning surgery. The researchers then tested 30 heart tissue samples from a subgroup of patients from the RCT (14 from the morning surgery group and 16 from the afternoon surgery group). They found that the afternoon surgery samples more quickly regained their ability to contract when put in conditions that replicated the heart refilling with blood. A genetic analysis also showed that 287 genes linked to the circadian clock were more active in the afternoon surgery samples compared with the morning surgery samples. This suggests that the heart is subject to the body’s circadian clock, and the surgical outcomes reflect the heart’s poorer ability to repair in the morning than in the afternoon.

3D “scaffold” map to aid cancer treatment search

Researchers from the Walter and Eliza Hall Institute of Medical Research (WEHI) have produced the first three-dimensional map of a molecular “scaffold” called SgK223, known to play a critical role in the development and spread of aggressive breast, colon and pancreatic cancers. Armed with the map, the research team is looking at ways of targeting parts of the scaffold molecule critical for its function. They hope the research will lead to novel strategies to target cancer. The research was the result of a long-standing collaboration between researchers from WEHI, Monash University’s Biomedicine Research Institute, the Bio21 Institute at the University of Melbourne, and the Australian Synchrotron. The research was published in Nature Communications. Dr Isabelle Lucet from WEHI said that SgK223 was a member of a family of proteins called pseudokinases and had been classified for a long time as a “dead enzyme”. SgK223 is unique among pseudokinases because it acts as a molecular scaffold, facilitating the assembly of vital signalling molecules whose activities control the normal functions of a cell, such as cell shape and migration. “Because of its primary role in facilitating the assembly of signalling molecules, high levels of SgK223 can jeopardise the normal functions of a cell and contribute to changes that lead to cancer,” Dr Lucet said. “High levels of SgK223 have been found in some aggressive subtypes of breast, colon and pancreatic cancers, suggesting that SgK223 may be a target for novel anticancer therapies.”

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